Limbal epithelial stem cells are responsible for renewal of the corneal epithelium. When these cells become
dysfunctional or deficient, a disease called limbal stem cell deficiency (LSCD) develops which causes visual
impairment and reduced quality of life. LSCD afflicts thousands of patients in North America. In patients with
unilateral LSCD, limbal stem cells from the healthy fellow eye can be used for corneal surface reconstruction in
a procedure called conjunctival limbal autograft (CLAU). Although CLAU is successful in majority of cases with
unilateral LSCD, it carries the potential risk of causing LSCD in the donor cornea as two large pieces of the
limbus are conventionally harvested for the procedure. To circumvent this risk, a new technique has recently
been developed, so-called Cultivated Autologous Limbal Epithelial Cell (CALEC) transplantation. In this
technique, cells from a small area of the donor limbus are expanded in the laboratory before transplantation to
the diseased eye, minimizing the risk of damage to the donor cornea.
As there is no CALEC product available in the U.S., we have optimized and standardized the techniques of
CALEC preparation by removing antibiotics and murine feeder cells, and employing highly reproducible methods
for cell isolation, expansion and quality control of the resultant CALEC sheets. We have received Investigational
New Drug Application (IND #16102) approval from the FDA for our CALEC graft to perform a clinical trial at the
Massachusetts Eye and Ear Infirmary (MEEI), Boston, MA, for unilateral LSCD.
This is a single center study to assess safety and feasibility of CALEC grafts and to compare its efficacy to CLAU
in 24 patients with unilateral LSCD. Study design has been approved by the FDA. By showing the safety,
feasibility and efficacy of CALEC, this study will pave the way for widespread use of the CALEC transplantation
in patients with unilateral LSCD by sharing the technology with other institutions across the U.S.
This is a resubmission of a previously submitted U-10 grant. There are three companion UG-1 Cooperative
Agreements including Chair’s Grant, Coordinating Center Grant, and Resource Center Grant. In the Chair’s
Grant, Ula Jurkunas, MD, and Ahmad Kheirkhah, MD are the Principal Investigators who will be responsible for
the overall conduct of this study and for providing scientific, technical, and administrative leadership. MEEI will
be the Clinical Center which will be responsible for recruitment and retention of the study participants and
implementation of the study protocol. Coordinating Center Grant will be submitted by Jaeb Center for Health
Research, Tampa, FL, which will provide the scientific, statistical and methodological leadership, logistical
coordination and support for the study. Resource Center Grant will be submitted by Connell and O’Reilly Families
Cell Manipulation Core Facility (CMCF) at the Dana-Farber Cancer Institute, Boston, MA, which will manufacture
the CALEC graft. An NEI Program Officer will be involved for these Cooperative Agreements to assist the
Principal Investigators in all aspects of the study.
